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Journal Article

A photocleavable masked nuclear-receptor ligand enables temporal control of C. elegans development


Antebi,  A.
Department Antebi - Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Judkins, J. C., Mahanti, P., Hoffman, J. B., Yim, I., Antebi, A., & Schroeder, F. C. (2014). A photocleavable masked nuclear-receptor ligand enables temporal control of C. elegans development. Angew Chem Int Ed Engl, 53(8), 2110-3. doi:10.1002/anie.201307465.

Cite as: https://hdl.handle.net/21.11116/0000-000B-83A2-9
The development and lifespan of C. elegans are controlled by the nuclear hormone receptor DAF-12, an important model for the vertebrate vitamin D and liver X receptors. As with its mammalian homologues, DAF-12 function is regulated by bile acid-like steroidal ligands; however, tools for investigating their biosynthesis and function in vivo are lacking. A flexible synthesis for DAF-12 ligands and masked ligand derivatives that enable precise temporal control of DAF-12 function was developed. For ligand masking, photocleavable amides of 5-methoxy-N-methyl-2-nitroaniline (MMNA) were introduced. MMNA-masked ligands are bioavailable and after incorporation into the worm, brief UV irradiation can be used to trigger the expression of DAF-12 target genes and initiate development from dauer larvae into adults. The in vivo release of DAF-12 ligands and other small-molecule signals by using photocleavable MMNA-masked ligands will enable functional studies with precise spatial and temporal resolution.